HLA-B57 does not fully explain the ability of HIV controllers to clear HCV infection

Alice K. Asher1, RN, MS; Glenn-Milo Santos1, MPH; Jennifer Evans, MS1; E. Kainne Dokubo1, MD; Jeff Martin1, MD; Steve Deeks1, MD; MPH; Leslie Tobler2, Dr.Ph; Mike Busch2, MD, Ph.D.; Peter Hunt1, MD; Kimberly Page1, PhD, MPH 1University of California, San Francisco2Blood Systems Research Institute, San Francisco, California

Spontaneous clearance of HCV

• 20-25% of HCV infected persons spontaneously clear the virus

• HIV co-infected: 10-20%• Factors associated with

spontaneous HCV clearance:– Sex (Micallef, et al., 2007; Page, et al., 2009)

– IL-28B status (Thomas, et al., 2009)

– HLA type (Thio, et al., 2002; Kim, et al., 2011)

– T cell response (Osburn, et al., 2010)

• Micallef, 2007, J. Viral Hepatitis; Matthews, 2008, Gasterenterol Hepatol

HIV control in the absence of ART

• 1-5% of PLWHA are considered ‘HIV controllers’

• Elite controllers: anti-HIV positive; no measurable HIV viremia (<75 copies/mL)

• Viremic controllers: anti-HIV positive; measurable low level viremia (75-2000 copies/mL)

• HIV controllers are more likely to spontaneously clear HCV

• Deeks, 2007, Immunity.

• Sadaji, 2010, AIDS; Salgado, 2011, AIDS; Kim, 2011, Gasteroenterology

Host genetic polymorphisms associated with HIV and HCV outcomesGene HIV association HCV association

HLA-B*57 Viral control(Migueles et al, PNAS

2000)

Increased clearance(Thio et al, JV 2002)

HLA-Cw*04

More rapid HIV progression

(Carrington et al, Science 1999)

Decreased clearance(Thio et al, JV 2002)

IL28B (CC)

Association with higher all-cause

mortality (Parczewski et al,

AIDS Research and Human Retroviruses

2012)

Increased clearance(Thomas et al, Nature

2009)

Objective

1) Assess relationship between spontaneous control of HIV and HCV clearance

2) Assess host genetic factors that may explain HCV clearance in HIV controllers

Methods

• Participants sampled from SCOPE cohort– >1600 chronically HIV+ patients– Enriched for HIV controllers– HLA typing available

• Included: HCV Ab+ (Ortho Clinical Diagnostics®)

• Excluded: HBsAg+, Hx of HCV treatment

• HCV RNA using discriminatory TMA (Novartis®)

• Spontaneous HCV clearance: HCVAb+/RNA-

• IL28B genotyping performed

Study population (N=279)

Non-controllers

N (%)N=231

HIV controllers†

N (%)N=48

Sex

Female (%) 66 (29) 14 (29)

Age (Median IQR)

40 (36-46) 41 (37-48)

Race

Caucasian (%) 97 (42) 18 (38)

Elite controllers + HIV viremic controllers (<2000 copies/ML without ART for at least 12 months†

8

HCV clearance by HIV controller status

9

HCV clearance by HIV controller status

Differences significant when adjusted for sex, age & race (APR 1.44, p=0.026)

Genetic polymorphisms in HIV controllers and non-controllers

HIV Non-controllers

N (%)N=231

HIV controllers

N (%)N=48

p-value

HLA B*57 24 (10) 16 (33) <0.001*

HLA Cw*04 59 (26) 8 (17) 0.19

IL28B (CC) 89 (39) 12 (48) 0.49

11

HCV clearance by HLA B*57 and HIV controller status

P=0.004

12

HCV clearance by HLA B*57 and HIV controller status

P for interaction =0.01

P=0.004

Conclusions• HIV controllers are more likely to clear

HCV infection than non-controllers• While HLA B*57 predicts HCV clearance

in HIV non-controllers, it does not fully explain HCV clearance in HIV controllers– >50% B*57- HIV controllers clear HCV

• Host factors other than HLA B*57 contribute to the control of HCV in HIV controllers

• Identifying these factors may support the development of novel vaccine strategies for HIV and HCV

Special Thanks• SCOPE Study:

– Peter Hunt, MD

– Melissa Krone

– Jeff Martin, MD

– Steve Deeks, MD

• Kimberly Page, Ph.D., M.P.H.

• Milo Santos, M.P.H.

• Jennifer Evans, M.S.

• Meghan Morris, Ph.D.

• E. Kainne Dokubo, MD

• Blood Systems Research Institute:

– Leslie Tobler, Dr.Ph

– Mike Busch, MD, Ph.D.

– Tzong-Hae Lee, MD, Ph.D.